RESUMEN
BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2â¯years. On-site rapid HCV antibody testing was integrated after 1â¯year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (nâ¯=â¯11,993 recruited at baseline; nâ¯=â¯11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Prestación Integrada de Atención de Salud/métodos , VIH , Hepacivirus/inmunología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adulto , Análisis por Conglomerados , Comorbilidad , Estudios Transversales , Femenino , Reducción del Daño , Hepatitis C/sangre , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/sangre , Humanos , India/epidemiología , Masculino , Prevalencia , Minorías Sexuales y de Género , Adulto JovenRESUMEN
HIV-1 subtype C (HIV-1C) may duplicate longer amino acid stretches in the p6 Gag protein, leading to the creation of an additional Pro-Thr/Ser-Ala-Pro (PTAP) motif necessary for viral packaging. However, the biological significance of a duplication of the PTAP motif for HIV-1 replication and pathogenesis has not been experimentally validated. In a longitudinal study of two different clinical cohorts of select HIV-1 seropositive, drug-naive individuals from India, we found that 8 of 50 of these individuals harbored a mixed infection of viral strains discordant for the PTAP duplication. Conventional and next-generation sequencing of six primary viral quasispecies at multiple time points disclosed that in a mixed infection, the viral strains containing the PTAP duplication dominated the infection. The dominance of the double-PTAP viral strains over a genetically similar single-PTAP viral clone was confirmed in viral proliferation and pairwise competition assays. Of note, in the proximity ligation assay, double-PTAP Gag proteins exhibited a significantly enhanced interaction with the host protein tumor susceptibility gene 101 (Tsg101). Moreover, Tsg101 overexpression resulted in a biphasic effect on HIV-1C proliferation, an enhanced effect at low concentration and an inhibitory effect only at higher concentrations, unlike a uniformly inhibitory effect on subtype B strains. In summary, our results indicate that the duplication of the PTAP motif in the p6 Gag protein enhances the replication fitness of HIV-1C by engaging the Tsg101 host protein with a higher affinity. Our results have implications for HIV-1 pathogenesis, especially of HIV-1C.
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Proteínas de Unión al ADN/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/fisiología , Factores de Transcripción/metabolismo , Replicación Viral , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo , Adulto , Secuencias de Aminoácidos , Células Cultivadas , Proteínas de Unión al ADN/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Femenino , Infecciones por VIH/genética , VIH-1/química , VIH-1/genética , Interacciones Huésped-Patógeno , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mapas de Interacción de Proteínas , Factores de Transcripción/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/química , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
Men who have sex with men (MSM) remain at high risk for HIV infection. Culturally specific sexual identities, encompassing sexual roles, behavior, and appearance, may shape MSM's experiences of stigmatization and discrimination, and affect their vulnerability to HIV. This multi-site qualitative study (n = 363) encompassing 31 focus group discussions (FGDs) and 121 in-depth interviews (IDIs) across 15 sites in India investigated sexual identity formation, identity practices, and transitions and their implications for HIV prevention. IDIs and FGDs were transcribed, translated, and underwent thematic analysis. Our findings document heterogeneous sexual identity formation, with MSM who have more gender nonconforming behaviors or appearance reporting greater family- and community-level disapproval, harassment, violence, and exclusion. Concealing feminine aspects of sexual identities was important in daily life, especially for married MSM. Some participants negotiated their identity practices in accordance with socioeconomic and cultural pressures, including taking on identity characteristics to suit consumer demand in sex work and on extended periods of joining communities of hijras (sometimes called TG or transgender women). Participants also reported that some MSM transition toward more feminine and hijra or transgender women identities, motivated by intersecting desires for feminine gender expression and by social exclusion and economic marginalization. Future studies should collect information on gender nonconformity stigma, and any changes in sexual identity practices or plans for transitions to other identities over time, in relation to HIV risk behaviors and outcomes.
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Identidad de Género , Homosexualidad Masculina/psicología , Conducta Sexual , Femenino , Grupos Focales , Infecciones por VIH , Humanos , India , Masculino , Trabajo Sexual , TransexualidadRESUMEN
BACKGROUND & OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs) are known to cause mitochondrial toxicity. This study was done to estimate mitochondrial DNA (mtDNA) content of peripheral blood mononuclear cells (PBMCs) among human immunodeficiency virus (HIV) infected, NRTI treated and antiretroviral therapy (ART)-naïve patients and evaluate the utility of mtDNA content as a biomarker of mitochondrial toxicity. METHODS: mtDNA content in PBMCs of 57 HIV-infected ART untreated and 30 ART treated with stavudine (d4T) or zidovudine (AZT) containing regimen were compared against 24 low-risk healthy controls (LoRHC). RESULTS: There was a significant (P=0.01) reduction in mtDNA content among HIV-infected (104; 80-135) compared to LoRHC (127; 110-167), and it was the same in both the treated (104.8; 88-130) and untreated patients (104.7; 78-142). mtDNA significantly (P=0.014) declined in ART treated patients symptomatic for toxicity (97; 74-111) than the asymptomatic patients (128; 103- 153). INTERPRETATION & CONCLUSIONS: mtDNA depletion in PBMCs was evident among HIV-infected individuals on ART. Moreover, as mtDNA content was reduced among the patients symptomatic for toxicity than the asymptomatic in both the HIV-infected groups, the current study supports mtDNA content of PBMCs to serve as a biomarker of mitochondrial dysfunction induced by NRTI and HIV. Longitudinal studies with a large sample need to be done to confirm these findings.
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ADN Mitocondrial/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adulto , Terapia Antirretroviral Altamente Activa , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/patogenicidad , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Estavudina/administración & dosificación , Estavudina/efectos adversos , Zidovudina/administración & dosificaciónRESUMEN
UNLABELLED: Broadly neutralizing antibodies isolated from infected patients who are elite neutralizers have identified targets on HIV-1 envelope (Env) glycoprotein that are vulnerable to antibody neutralization; however, it is not known whether infection established by the majority of the circulating clade C strains in Indian patients elicit neutralizing antibody responses against any of the known targets. In the present study, we examined the specificity of a broad and potent cross-neutralizing plasma obtained from an Indian elite neutralizer infected with HIV-1 clade C. This plasma neutralized 53/57 (93%) HIV pseudoviruses prepared with Env from distinct HIV clades of different geographical origins. Mapping studies using gp120 core protein, single-residue knockout mutants, and chimeric viruses revealed that G37080 broadly cross-neutralizing (BCN) plasma lacks specificities to the CD4 binding site, gp41 membrane-proximal external region, N160 and N332 glycans, and R166 and K169 in the V1-V3 region and are known predominant targets for BCN antibodies. Depletion of G37080 plasma with soluble trimeric BG505-SOSIP.664 Env (but with neither monomeric gp120 nor clade C membrane-proximal external region peptides) resulted in significant reduction of virus neutralization, suggesting that G37080 BCN antibodies mainly target epitopes on cleaved trimeric Env. Further examination of autologous circulating Envs revealed the association of mutation of residues in the V1 loop that contributed to neutralization resistance. In summary, we report the identification of plasma antibodies from a clade C-infected elite neutralizer that mediate neutralization breadth via epitopes on trimeric gp120 not yet reported and confer autologous neutralization escape via mutation of residues in the V1 loop. IMPORTANCE: A preventive vaccine to protect against HIV-1 is urgently needed. HIV-1 envelope glycoproteins are targets of neutralizing antibodies and represent a key component for immunogen design. The mapping of epitopes on viral envelopes vulnerable to immune evasion will aid in defining targets of vaccine immunogens. We identified novel conformational epitopes on the viral envelope targeted by broadly cross-neutralizing antibodies elicited in natural infection in an elite neutralizer infected with HIV-1 clade C. Our data extend our knowledge on neutralizing epitopes associated with virus escape and potentially contribute to immunogen design and antibody-based prophylactic therapy.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Anti-VIH/sangre , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Evasión Inmune/inmunología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , Vacunas contra el SIDA/inmunología , Línea Celular , Mapeo Epitopo , Epítopos/inmunología , Células HEK293 , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/virología , Humanos , IndiaRESUMEN
BACKGROUND: HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study. METHODS: In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C. RESULTS: In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24-36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years. CONCLUSION: We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1.
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Infecciones por VIH/epidemiología , VIH-1/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Adulto , Femenino , Estudios de Seguimiento , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , India/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/análisis , Sudáfrica/epidemiología , Adulto JovenRESUMEN
The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332 specificity. Pseudotyped viruses expressing autologous envs were found to be resistant to autologous BCN plasma as well as to PGT121 and PGT128 mAbs despite the majority of Envs containing an intact N332 residue. While resistance of one of the Envs to neutralization by autologous plasma antibodies with shorter V1 loop length was found to be correlated with a N332S mutation, resistance to neutralization of rest of the Envs was found to be associated with longer V1 loop length and acquisition of protective N-glycans. In summary, we show evidence of escape of circulating HIV-1 clade C in an individual from autologous BCN antibodies by three distinct mechanisms.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Anti-VIH/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Fragmentos de Péptidos/inmunología , Polisacáridos/inmunología , Anticuerpos Anti-VIH/química , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/virología , VIH-1/genética , VIH-1/fisiología , Humanos , Mutación , Pruebas de Neutralización , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunologíaRESUMEN
Poor psychosocial health contributes to HIV risk behavior and reduced engagement in treatment and care. This study investigates depression and its correlates among 11,992 MSM recruited via respondent driven sampling in 12 cities across India using the Patient Health Questionnaire-9 and supplemented by analysis of qualitative research from 15 sites with 363 MSM. Overall prevalence of depression was 11 %, with substantial variation across sites and subgroups of MSM, and high prevalence of suicidal thoughts among depressed MSM. In multivariable analyses identification as a kothi (feminine sexual identity) [adjusted odds ratio (aOR) = 1.91], disclosure of being MSM to non-family (aOR = 1.7) and family (aOR = 2.4), disclosure of HIV-status (aOR = 5.6), and substance use were associated with significantly higher odds of depression. Qualitative results emphasized dire social consequences of disclosing MSM- and HIV-status, especially to family, including suicidality. Combination prevention interventions should include mental health services that address disclosure, suicidality, and substance use.
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Depresión/epidemiología , Infecciones por VIH/etnología , Homosexualidad Masculina/psicología , Estigma Social , Suicidio/etnología , Adolescente , Adulto , Estudios Transversales , Depresión/psicología , Infecciones por VIH/psicología , Homosexualidad Masculina/etnología , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Investigación Cualitativa , Apoyo Social , Trastornos Relacionados con Sustancias/epidemiología , Suicidio/psicología , Encuestas y Cuestionarios , Revelación de la Verdad , Población Urbana , Adulto JovenRESUMEN
UNAIDS set an ambitious target of "90-90-90" by 2020. The first 90 being 90% of those HIV-infected will be diagnosed; the second 90 being 90% of those diagnosed will be linked to medical care and on antiretroviral therapy (ART). While there has been dramatic improvement in HIV testing and ART use, substantial losses continue to occur at linkage-to-care following HIV diagnosis. Data on linkage among men who have sex with men (MSM) and people who inject drugs (PWID) are sparse, despite a greater burden of HIV in these populations. This cross-sectional study was conducted in 27 sites across India. Participants were recruited using respondent-driven sampling and had to be ≥18 years and self-identify as male and report sex with a man in the prior year (MSM) or injection drug use in the prior 2 years (PWID). Analyses were restricted to HIV-infected persons aware of their status. Linkage was defined as ever visiting a doctor for management of HIV after diagnosis. We explored factors that discriminated between those linked and not linked to care using multi-level logistic regression and area under the receiver operating curves (AUC), focusing on modifiable factors. Of 1726 HIV-infected persons aware of their status, 80% were linked to care. Modifiable factors around the time of diagnosis that best discriminated linkage included receiving assistance with HIV medical care (odds ratio [OR]: 10.0, 95% confidence interval [CI]): 5.6-18.2), disclosure of HIV-positive status (OR: 2.8; 95% CI: 2.4-6.1) and receiving information and counseling on management of HIV (OR: 2.3; 95% CI: 1.1-4.6). The AUC for these three factors together was 0.85, higher than other combinations of factors. We identified three simple modifiable factors around the time of diagnosis that could facilitate linkage to care among MSM and PWID in low- and middle-income countries to achieve UNAIDS targets.
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Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina/estadística & datos numéricos , Aceptación de la Atención de Salud , Abuso de Sustancias por Vía Intravenosa , Adulto , Estudios Transversales , Consejo Dirigido , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , India , Masculino , Educación del Paciente como Asunto , Abuso de Sustancias por Vía Intravenosa/epidemiología , Revelación de la Verdad , Adulto JovenRESUMEN
BACKGROUND: Childhood sexual abuse (CSA) is a significant global public health problem, which is associated with negative psychosocial outcomes and high-risk sexual behaviors in adults. Men who have sex with men (MSM) often report higher prevalence of CSA history than the general population, and CSA may play a key role in MSM's greater vulnerability to HIV. METHODS: This study examined the prevalence of CSA history and its impact on the number of recent HIV-related risk behaviors (unprotected anal intercourse, high number of male and female sexual partners, alcohol use, drug use, and sex work in prior 6 months) and lifetime risk behaviors and experiences (high number of lifetime male and female sexual partners, early sexual debut, injection drug use, sex work, and intimate partner violence) among 11,788 adult MSM recruited via respondent driven sampling across 12 sites in India, with additional insights from thematic analysis of qualitative research with 363 MSM from 15 sites. RESULTS: Nearly a quarter (22.4 %) of participants experienced CSA, with substantially higher prevalence of CSA in the South and among kothis (feminine sexual identity). Qualitative findings revealed that older, trusted men may target young and, especially, gender nonconforming boys, and perpetrators' social position facilitates nondisclosure. CSA may also initiate further same-sex encounters, including sex work. In multivariable analysis, MSM who experienced CSA had 21 % higher rate of recent (adjusted rate ratio [aRR = 1.21], 95 % confidence interval [CI]: 1.14-1.28), and 2.0 times higher lifetime (aRR = 2.04, 95 % CI: 1.75-2.38) HIV-related behaviors/experiences compared with those who did not. CONCLUSION: This large, mixed-methods study found high overall prevalence of CSA among MSM (22.4 %), with substantially higher prevalence among MSM residing in the South and among more feminine sexual identities. Qualitative findings highlighted boys' vulnerabilities to CSA, especially gender nonconformity, and CSA's role in further sexual encounters, including sex work. Additionally, CSA was associated with an elevated rate of recent, and an even higher rate of lifetime HIV-related risk factors. Our results suggest an acute need for the development of CSA prevention interventions and the integration of mental health services for MSM with histories of CSA as part of HIV-prevention efforts.
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Abuso Sexual Infantil , Infecciones por VIH/etiología , Homosexualidad Masculina , Asunción de Riesgos , Conducta Sexual , Adolescente , Adulto , Niño , Abuso Sexual Infantil/psicología , Abuso Sexual Infantil/estadística & datos numéricos , Identidad de Género , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Homosexualidad Masculina/psicología , Humanos , India/epidemiología , Violencia de Pareja , Masculino , Análisis Multivariante , Prevalencia , Investigación Cualitativa , Trabajo Sexual , Parejas Sexuales , Trastornos Relacionados con Sustancias/etiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Globally, men who have sex with men and people who inject drugs remain disproportionately affected by HIV, but they have not been the focus of prevention and treatment interventions in many resource-limited settings. METHODS/DESIGN: This cluster-randomized trial (conducted from June 2012 to June 2017), evaluates whether single-venue, integrated delivery of core HIV services to vulnerable high-risk populations improves service utilization and consequently, HIV testing and other outcomes along the HIV care continuum. Core services include: HIV counseling and testing, information, education and communication, condom distribution, needle and syringe exchange programs, opioid agonist therapy, management of sexually transmitted infections, tuberculosis screening, diagnosis, and treatment, and antiretroviral therapy. Stratified restricted randomization was used to allocate 22 Indian cities (10 men who have sex with men and 12 people who inject drugs sites) at a 1:1 ratio to either the intervention or control condition. Integrated care centers were scaled-up and implemented in the 11 intervention cities and outcomes will be assessed by pre- and post-intervention surveys at intervention and control sites. As men who have sex with men and people who inject drugs are hidden populations, with no sampling frame, respondent-driven sampling will be used to accrue samples for the two independent cross-sectional surveys. DISCUSSION: For an AIDS-free generation to be realized, prevention, care and treatment services need to reach all populations at risk for HIV infection. There is a clear gap in access to services among men who have sex with men and people who inject drugs. Trials need to be designed to optimize utilization of services in these populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01686750 Date of Registration: September 13, 2012.
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Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Abuso de Sustancias por Vía Intravenosa/rehabilitación , Adolescente , Adulto , Anciano , Ciudades , Centros Comunitarios de Salud/normas , Continuidad de la Atención al Paciente/normas , Consejo , Estudios Transversales , Prestación Integrada de Atención de Salud/normas , Humanos , India , Masculino , Tamizaje Masivo/psicología , Persona de Mediana Edad , Asunción de Riesgos , Enfermedades de Transmisión Sexual/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: We characterize the human immunodeficiency virus (HIV) care continuum for men who have sex with men (MSM) and persons who inject drugs (PWID) across India. METHODS: We recruited 12 022 MSM and 14 481 PWID across 26 Indian cities, using respondent-driven sampling (September 2012 to December 2013). Participants were aged ≥18 years and either self-identified as male and reported sex with a man in the prior year (MSM) or reported injection drug use in the prior 2 years (PWID). Correlates of awareness of HIV-positive status were characterized using multilevel logistic regression. RESULTS: A total of 1146 MSM were HIV infected, of whom a median of 30% were aware of their HIV-positive status, 23% were linked to care, 22% were retained before antiretroviral therapy (ART), 16% had started ART, 16% were currently receiving ART, and 10% had suppressed viral loads. There was site variability (awareness range, 0%-90%; suppressed viral load range, 0%-58%). A total of 2906 PWID were HIV infected, of whom a median of 41% were aware, 36% were linked to care, 31% were retained before ART, 20% had started ART, 18% were currently receiving ART, and 15% had suppressed viral loads. Similar site variability was observed (awareness range: 2%-93%; suppressed viral load range: 0%-47%). Factors significantly associated with awareness were region, older age, being married (MSM) or female (PWID), use of other services (PWID), more lifetime sexual partners (MSM), and needle sharing (PWID). Ongoing injection drug use (PWID) and alcohol use (MSM) were associated with lower awareness. CONCLUSIONS: In this large sample, the major barrier to HIV care engagement was awareness of HIV-positive status. Efforts should focus on linking HIV testing to other essential services. CLINICAL TRIALS REGISTRATION: NCT01686750.
Asunto(s)
Continuidad de la Atención al Paciente , Infecciones por VIH/diagnóstico , Infecciones por VIH/terapia , Homosexualidad Masculina , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , India/epidemiología , Masculino , Compartición de Agujas , Factores de Riesgo , Asunción de Riesgos , Parejas SexualesRESUMEN
Traditional recruitment methods for microbicide efficacy trials are labor intensive and may fail to reach high-risk hard-to-reach populations. We report duration of recruitment and lessons learned from a two-stage process to recruit female sex workers (FSWs) into a placebo microbicide trial, and examined characteristics associated with successful recruitment of peers who screened for and enrolled in the trial. FSWs were first recruited via respondent-driven sampling (RDS) to complete a survey and subsequently invited to screen for enrollment into a placebo microbicide trial taking place at a local clinic. It took 6 months to enroll 267 participants into the trial. Successful recruiters of peers who enrolled were more likely to have enrolled themselves (AOR 2.0, CI 1.3-2.9) and less likely to visit Nellore city (AOR 0.5, CI 0.3-0.9). Recruitment of FSWs via a two-stage recruitment strategy with RDS can be a good option for future clinical trials.
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Antiinfecciosos Locales/administración & dosificación , Infecciones por VIH/prevención & control , Encuestas Epidemiológicas/métodos , Selección de Paciente , Trabajadores Sexuales/estadística & datos numéricos , Cremas, Espumas y Geles Vaginales/administración & dosificación , Adolescente , Adulto , Femenino , Infecciones por VIH/psicología , Humanos , India/epidemiología , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Muestreo , Trabajo Sexual , Trabajadores Sexuales/psicología , Factores de TiempoRESUMEN
BACKGROUND: Drug users (DUs), a population that accounts for some of the fastest-growing human immunodeficiency virus (HIV) epidemics globally, lag behind other populations with regard to HIV-related outcomes. We evaluated the role of voucher incentives on linkage and retention in care among DUs in India. METHODS: In this randomized clinical trial, 120 DUs who were aged ≥18 years, HIV-infected, antiretroviral therapy (ART) naive, and ART eligible and who reported drug use in the prior month were randomized to incentive (INC) or control (CTL) conditions for 12 months. Participants randomized to the INC arm received incentives (redeemable for food/household goods) ranging in value from USD4 to USD8 for achieving prespecified targets (eg, ART initiation, visits to ART center). Subjects in the CTL group could win vouchers in prize-bowl drawings, but HIV care behaviors were not incentivized. The primary endpoint was time to ART initiation. RESULTS: Sixty participants each were randomized to the INC and CTL arms between December 2009 and September 2010. Participants in the INC arm were more likely to visit the government ART center (49 vs 33; P = .002); 27 participants in the INC and 16 participants in the CTL arm initiated ART (P = .04; hazard ratio for ART = 2.33 [95% confidence interval, 1.15-4.73]). Participants in the INC arm also had significantly more visits to the ART center (median number of visits, 8 vs 3.5; P = .005). However, no difference in viral suppression was observed. CONCLUSIONS: Modest voucher incentives improved linkage to and retention in HIV care, but did not significantly impact viral suppression among DUs in India, a disenfranchised and difficult-to-treat population. CLINICAL TRIALS REGISTRATION: NCT01031745.
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Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Consumidores de Drogas , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación , Motivación , Adulto , Femenino , VIH/aislamiento & purificación , Humanos , India , Masculino , Carga ViralRESUMEN
OBJECTIVES: Several recent studies suggest that intermediate vaginal flora (IVF) is associated with similar adverse health outcomes as bacterial vaginosis (BV). Yet, it is still unknown if IVF and BV share the same correlates. We conducted a cross-sectional and exploratory analysis of data from women screened prior to enrolment in a microbicide trial to estimate BV and IVF prevalence and examine their respective correlates. METHODS: Participants were interviewed, examined and provided blood and genital samples for the diagnosis of IVF and BV (using Nugent score) and other reproductive tract infections. Polytomous logistic regressions were used in estimating respective ORs of IVF and BV, in relation to each potential risk factor. RESULTS: Among 1367 women, BV and IVF prevalences were 47.6% (95% CI 45.0% to 50.3%) and 19.2% (95% CI 17.1% to 21.2%), respectively. Multivariate polytomous analysis of IVF and BV showed that they were generally associated with the same factors. The respective adjusted ORs were for HIV 1.98 (95% CI 1.37 to 2.86) and 1.62 (95% CI 1.20 to 2.20) (p=0.2248), for gonorrhoea 1.25 (95% CI 0.64 to 2.4) and 2.01 (95% CI 1.19 to 3.49) (p=0.0906), for trichomoniasis 3.26 (95% CI 1.71 to 6.31) and 2.39 (95% CI 1.37 to 4.33) (p=0.2630), for candidiasis 0.52 (95% CI 0.36 to 0.75) and 0.59 (95% CI 0.44 to 0.78) (p=0.5288), and for hormonal contraception 0.65 (95% CI 0.40 to 1.04) and 0.62 (95% CI 0.43 to 0.90) (p=0.8819). In addition, the association between vaginal flora abnormalities and factors such as younger age, HIV, gonorrhoea trichomoniasis and candidiasis were modified by the study site (all p for interaction ≤0.05). CONCLUSIONS: IVF has almost the same correlates as BV. The relationship between some factors and vaginal flora abnormalities may be site-specific.
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Candidiasis/microbiología , Gonorrea/microbiología , Infecciones por VIH/microbiología , Trabajadores Sexuales , Vagina/microbiología , Vaginosis Bacteriana/microbiología , Adulto , África , Factores de Edad , Antiinfecciosos/uso terapéutico , Candidiasis/epidemiología , Candidiasis/inmunología , Estudios Transversales , Femenino , Gonorrea/epidemiología , Gonorrea/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Humanos , India , Prevalencia , Factores de Riesgo , Vagina/inmunología , Vaginosis Bacteriana/epidemiología , Vaginosis Bacteriana/inmunologíaRESUMEN
Long-term follow-up of persons infected with HIV infection is essential to optimize clinical outcomes. However, limited data exist on the rates of dropout (DO) from HIV care and factors associated with DO especially from resource-limited settings. We conducted a retrospective analysis of the data available at YRGCARE, a private HIV care provider in south India that has registered over 15,000 HIV-infected persons since its inception in 1993. We included 7995 patients who registered for care between 1 January 2004 and 31 December 2009. A dropout was defined as a person who registered for care during this period and had not been seen in the clinic for >1 year. Logistic regression was used to examine factors associated with DO from clinical care. The median age of the patients registered for care was 34 years; 66% were male and 83% were married. The overall DO rate was 38.1 per 100 person-years - the majority of the DOs occurred within 6 months from registration. In multivariate analyses, patients who were enrolled in clinical studies/projects entitling them to free medications and retention staff (Odds Ratio [OR]: 0.65) or were on antiretroviral therapy (ART; OR: 0.37) or had a CD4 > 350 at the last visit (OR: 0.20) were significantly less likely to DO from clinical care. We observed a high rate of DO from clinical care at this tertiary HIV clinic in Chennai, India. Making ART available free of charge in the private sector and providing incentives/benefits for attending clinic visits as is routinely done in clinical trials might help improve retention.
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Atención Ambulatoria/estadística & datos numéricos , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , Femenino , Estudios de Seguimiento , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
We demonstrate that at least three different promoter variant strains of HIV-1 subtype C have been gradually expanding and replacing the standard subtype C viruses in India, and possibly in South Africa and other global regions, over the past decade. The new viral strains contain an additional NF-κB, NF-κB-like, or RBEIII site in the viral promoter. Although the acquisition of an additional RBEIII site is a property shared by all the HIV-1 subtypes, acquiring an additional NF-κB site remains an exclusive property of subtype C. The acquired κB site is genetically distinct, binds the p50-p65 heterodimer, and strengthens the viral promoter at the levels of transcription initiation and elongation. The 4-κB viruses dominate the 3-κB "isogenic" viral strains in pairwise competition assays in T-cell lines, primary cells, and the ecotropic human immunodeficiency virus mouse model. The dominance of the 4-κB viral strains is also evident in the natural context when the subjects are coinfected with κB-variant viral strains. The mean plasma viral loads, but not CD4 counts, are significantly different in 4-κB infection suggesting that these newly emerging strains are probably more infectious. It is possible that higher plasma viral loads underlie selective transmission of the 4-κB viral strains. Several publications previously reported duplication or deletion of diverse transcription factor-binding sites in the viral promoter. Unlike previous reports, our study provides experimental evidence that the new viral strains gained a potential selective advantage as a consequence of the acquired transcription factor-binding sites and importantly that these strains have been expanding at the population level.
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Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Duplicado del Terminal Largo de VIH , VIH-1/genética , FN-kappa B/metabolismo , Transcripción Genética , Adulto , Estudios de Cohortes , Femenino , Regulación Viral de la Expresión Génica , Infecciones por VIH/genética , VIH-1/química , VIH-1/clasificación , VIH-1/fisiología , Humanos , Masculino , Datos de Secuencia Molecular , FN-kappa B/genética , Unión Proteica , Replicación Viral , Adulto JovenRESUMEN
Respondent-driven sampling was used to recruit female sex workers (FSWs) for a community survey conducted in southern India. After survey completion, participants were given a brochure describing a clinical trial that entailed daily use of a placebo vaginal gel for four months. This study assessed predictors of screening among survey respondents, predictors of enrollment among those eligible for the trial, and predictors of visit attendance and retention among those enrolled. FSWs who reported having symptoms of sexually transmitted infections (STI), engaging in sex work in the past month, and living in a subdistrict easily accessible by public transportation with a high concentration of FSWs, were more likely to screen. FSWs who had never been tested for HIV were more likely to enroll. This analysis suggests that the primary reason FSWs participated in the trial was a desire for health care-not other factors hypothesized to be important, e.g., HIV risk perception and poverty status.
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Antiinfecciosos Locales/administración & dosificación , Infecciones por VIH/prevención & control , Tamizaje Masivo/estadística & datos numéricos , Trabajadores Sexuales/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Cremas, Espumas y Geles Vaginales/administración & dosificación , Adolescente , Adulto , Servicios de Salud Comunitaria , Escolaridad , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Encuestas Epidemiológicas , Humanos , India/epidemiología , Persona de Mediana Edad , Aceptación de la Atención de Salud , Selección de Paciente , Trabajadores Sexuales/psicología , Conducta Sexual/psicología , Clase Social , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Female sex workers (FSWs) were recruited for a 4-month placebo vaginal gel trial in Nellore, India. Two experiments explored if prior knowledge of biomarkers for unprotected sex and insertion of gel applicators would yield more accurate self-reports. A third experiment compared self-reports of gel use and adherence levels between FSWs randomly assigned to interactive voice response survey (IVRS) and those assigned to paper diaries. Prior knowledge of biomarkers did not improve accuracy of self-reported condom or gel use, nor did it affect actual adherence. Of those who tested positive for the presence of semenogelin in the vagina, 76% reported no unprotected sex in the previous 48 h. Overall, women reported using gel on 90% of days whereas the biomarker indicated gel use on fewer than 50% of days. Compliance to IVRS was low, despite familiarity with mobile phone technology. Additional explorations with other populations are needed.
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Cumplimiento de la Medicación , Cremas, Espumas y Geles Vaginales/uso terapéutico , Administración Intravaginal , Adolescente , Adulto , Antiinfecciosos/uso terapéutico , Biomarcadores/análisis , Femenino , Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Humanos , India , Persona de Mediana Edad , Autoinforme , Trabajadores Sexuales , Sexo Inseguro/prevención & control , Sexo Inseguro/estadística & datos numéricos , Adulto JovenRESUMEN
Nagpur is an industrial hub in Maharashtra, a state in Central India that has the second highest HIV prevalence in the country. Approximately 3000 brothel-based female sex workers (FSWs) are estimated to be working in Nagpur's Ganga-Jamuna red light district. The extent to which brothel madams, known as gharwalis, support HIV/STI prevention for FSWs has not been examined. The present study sought to identify personal, social, and behavioral characteristics of gharwalis in Nagpur as well as enhance our understanding of the gharwali's role in shaping the sexual practices of brothel-based FSWs. Thirty gharwalis participated in a survey that covered personal, social, behavioral, and environmental characteristics. Respondents ranged in age from 29 to 50 years (M = 38.9) and had worked as a gharwali for an average of 5.3 years; 80% had no formal education, 43% had never married, and 30% were divorced or separated, and 93% earned money from their own sex work. Gharwalis managed an average of 4.2 FSWs (range 2-10). Overall, gharwalis reported positive attitudes toward condoms, promoted use of condoms by their FSWs with clients, taught FSWs how to use condoms, knew where to obtain condoms for free, and required HIV testing for their FSWs; however, levels of HIV prevention knowledge were low. Gharwalis also reported providing a range of support services to FSWs who lived in their brothels, including shelter, protection from drunk and aggressive clients and police, emotional support, caring and love, and health care. These data suggest the feasibility of involving gharwalis in brothel-based HIV prevention programs.